Mark Davis, PhD, professor of microbiology and immunology and director of Stanford's Institute for Immunity, Transplantation and Infection, and his colleagues found that key immune cells in our bodies have "memories" of microbes they have never encountered. This casts doubt on the established dogma that the immune system develops a "memory" of a microbial pathogen, with a correspondingly enhanced readiness to combat that microbe, only upon exposure to it -- or to its components though a vaccine. The groundbreaking study was published online last Thursday in Immunity.
The researchers found that over the course of our lives, CD4 cells -- key players circulating in blood and lymph whose ability to kick-start the immune response to viral, bacterial, protozoan and fungal pathogens can spell the difference between life and death -- somehow acquire memory of microbes that have never entered our bodies. Investigators may now have to rethink the relevance of experiments conducted on mice in squeaky-clean facilities that have never been exposed to a single germ in their lives. Davis said that the study, "...may even provide an evolutionary clue about why kids eat dirt," and added that, "The pre-existing immune memory of dangerous pathogens our immune systems have never seen before might stem from our constant exposure to ubiquitous, mostly harmless micro-organisms in soil and food and on our skin, our doorknobs, our telephones and our iPod earbuds."
CD4 cells are members of the immune club known as T cells. They hang out in our circulatory system looking for micro-organisms that have found their way into the blood or lymph tissue. Our bodies have to host immensely diverse inventories of CD4 cells, each with its own capacity to recognize one single pathogenic "body part" or, scientifically speaking, epitope -- and, it has been believed, only that epitope. Contact with that epitope can make a CD4 replicate quickly and perform the immunological equivalent of posting notices, passing out ammunition and yelling attack orders through a microphone to other immune cells. This hyperactivity is necessary to the immune response.
Reshufflable "hot spots" in a rapidly dividing T cell's DNA trigger massive mixing-and-matching among these genetic components during cell division, so each resulting T cell sports its own unique variant of a crucial surface receptor. This makes it geared to recognizing a different epitope. That variation accounts for our ability to mount an immune response to all kinds of microbial invaders, whether familiar or previously unseen, but does not account for the immune memory phenomenon.
CD4 cells, like other T cells, can be divided into two groups: so-called "naïve" CD4s randomly targeting epitopes that belong to pathogens they have not yet encountered; and CD4s that, having had a prior run-in with one or another bug, have never forgotten it. These latter CD4 cells are long-lived and ultra-responsive to any new encounter with the same pathogen. William Petri, MD, PhD, chief of infectious diseases and international health at the University of Virginia said, "When a naïve CD4 cell comes across its target pathogen, it takes days or even weeks before the immune system is full mobilized against that pathogen. But an activated-memory CD4 cell can cause the immune system to mount a full-blown response within hours." Petri called the new study paradigm-shifting. "It was one of those rare, seminal findings that changes the way I think about the immune response," he said.
Source: ScienceDaily, 7 Feb. 2013. Web. 9 Feb. 2013.
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